Deuterated 1-piperazino-3-phenyl-indanes for treatment of schizophrenia have been disclosed in U.S. application Ser. No. 13/527,364. U.S. application Ser. No. 13/527,364 also discloses how specific deuterated 1-piperazino-3-phenyl-indanes can be obtained via 6-chloro-3-(phenyl-d5)-indan-1-one. However, the disclosed routes for synthesis of both racemic and enantiomerically pure 6-chloro-3-(phenyl-d5)-indan-1-one rely on the uneconomical use of high loading of either a chiral rhodium catalyst or a chiral palladium catalyst. Accordingly, new processes for the synthesis of racemic and enantiomerically pure 6-chloro-3-(phenyl-d5)-indan-1-one are desirable, and are herein described proceeding via the compound 6-chloro-3-(phenyl-d5)-inden-1-one (I).
Clark, W. M. et al in Organic Letter, 1999, Vol. 1, No. 11, pp. 1839-1842 attempted the preparation of 3-arylindenones, such as 6-chloro-3-(phenyl-d5)-indan-1-one (I), with electron-withdrawing groups (Cl, Br, NO2) at the C(5)- or C(6)-position of the indenone ring using a Suzuki methodology, but failed to obtain appreciable amounts of the desired products. In contrast, the present invention describes the successful preparation of such 3-arylindenones, e.g. 6-chloro-3-(phenyl-d5)-indan-1-one (I), via a Suzuki methodology.